The Low-Dose ACTH Test Does Not Identify Mild Insufficiency of the Hypothalamic-Pituitary-Adrenal Axis in Children with Inadequate Stress Response

ABSTRACT Objective: To investigate retrospectively the sensitivity of published cortisol cut-off points of the low-dose ACTH test (LDAT) in children with proven mild hypothalamic-pituitary-adrenal (HPA) axis insufficiency. Patients and Methods: The HPA axis of 11 pediatric patients (age range: 5.5-14.5 yr) with established mild HPA axis insufficiency was reinvestigated with the LDAT. The sensitivity of the LDAT was calculated on the basis of published stimulated cortisol cut-off points. Results: The LDAT showed both a significantly higher cortisol peak and a greater cortisol rise compared with the ITT (both P<0.01). The LDAT yielded a low sensitivity of 9-55 % using published cortisol cut-off points as references. Conclusion: Using published cortisol cut-off points, the LDAT showed a poor sensitivity to detect mild HPA axis insufficiency. We cannot recommend the use of the LDAT as a screening test of HPA axis impairment in such children.

[1]  E. Arvat,et al.  Hypothalamus–pituitary–adrenal axis evaluation in patients with hypothalamo–pituitary disorders: comparison of different provocative tests , 2008, Clinical endocrinology.

[2]  G. Reimondo,et al.  Secondary hypoadrenalism , 2008, Pituitary.

[3]  P. Stewart,et al.  The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis. , 2006, The Journal of clinical endocrinology and metabolism.

[4]  M. Maghnie,et al.  Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. , 2005, European journal of endocrinology.

[5]  E. Eugster,et al.  Prevalence of adrenocorticotropin deficiency in children with idiopathic growth hormone deficiency. , 2004, The Journal of clinical endocrinology and metabolism.

[6]  G. Binder,et al.  Insulin Tolerance Test Causes Hypokalaemia and Can Provoke Cardiac Arrhythmias , 2004, Hormone Research in Paediatrics.

[7]  A. Juul,et al.  High risk of adrenal insufficiency in adults previously treated for idiopathic childhood onset growth hormone deficiency. , 2003, The Journal of clinical endocrinology and metabolism.

[8]  N. Kandemir,et al.  Significance of Low-Dose and Standard-Dose ACTH Tests Compared to Overnight Metyrapone Test in the Diagnosis of Adrenal Insufficiency in Childhood , 2003, Hormone Research in Paediatrics.

[9]  C. Qualls,et al.  Diagnosis of Adrenal Insufficiency , 2003, Annals of Internal Medicine.

[10]  B. Walker,et al.  Ten years on: Safety of short synacthen tests in assessing adrenocorticotropin deficiency in clinical practice. , 2003, The Journal of clinical endocrinology and metabolism.

[11]  T. Mckenna,et al.  The low‐dose ACTH test does not provide a useful assessment of the hypothalamic–pituitary–adrenal axis in secondary adrenal insufficiency , 2002, Clinical endocrinology.

[12]  Y. Greenman,et al.  Low‐dose (1 μg) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo–pituitary–adrenal axis function: sensitivity, specificity and accuracy in comparison with the high‐dose (250 μg) test , 2000 .

[13]  Y. Greenman,et al.  Low-dose (1 microgram) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 microgram) test. , 2000, Clinical endocrinology.

[14]  J. Grice,et al.  Comparison of adrenocorticotropin (ACTH) stimulation tests and insulin hypoglycemia in normal humans: low dose, standard high dose, and 8-hour ACTH-(1-24) infusion tests. , 1999, The Journal of clinical endocrinology and metabolism.

[15]  R. Lustig,et al.  Diagnosis of ACTH Deficiency , 1999, Hormone Research in Paediatrics.

[16]  R. Clayton,et al.  Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. , 1999, The Journal of clinical endocrinology and metabolism.

[17]  R. Lustig,et al.  Diagnosis of ACTH deficiency. Comparison of overnight metyrapone test to either low-dose or high-dose ACTH test. , 1999, Hormone research.

[18]  B. Ambrosi,et al.  The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function. , 1998, European journal of endocrinology.

[19]  L. Blevins,et al.  The low dose (1-microg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency. , 1998, The Journal of clinical endocrinology and metabolism.

[20]  W. Oelkers,et al.  Comparison of Low and High Dose Corticotropin Stimulation Tests in Patients with Pituitary Disease , 1998 .

[21]  D. Lazard,et al.  Standard and low-dose short adrenocorticotropin test compared with insulin-induced hypoglycemia for assessment of the hypothalamic-pituitary-adrenal axis in children with idiopathic multiple pituitary hormone deficiencies. , 1998, The Journal of clinical endocrinology and metabolism.

[22]  R. Shankar,et al.  Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors. , 1997, The Journal of clinical endocrinology and metabolism.

[23]  S. Taback,et al.  Mortality in Canadian children with growth hormone (GH) deficiency receiving GH therapy 1967-1992. The Canadian Growth Hormone Advisory Committee. , 1996, The Journal of clinical endocrinology and metabolism.

[24]  S. Soule,et al.  Failure of the short ACTH test to unequivocally diagnose long‐standing symptomatic secondary hypoadrenalism , 1996, Clinical endocrinology.

[25]  E. Hägg,et al.  A low dose ACTH test to assess the function of the hypothalamic–pituitary–adrenal axis , 1996, Clinical endocrinology.

[26]  D. Streeten,et al.  The potential for serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test. , 1996, Journal of Clinical Endocrinology and Metabolism.

[27]  S. Grinspoon,et al.  Clinical review 62: Laboratory assessment of adrenal insufficiency. , 1994, The Journal of clinical endocrinology and metabolism.

[28]  L. Jonetz-Mentzel,et al.  Establishment of Reference Ranges for Cortisol in Neonates, Infants, Children and Adolescents , 1993, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[29]  Zusammenfassung,et al.  Longitudinale Körperentwicklung gesunder Kinder von 0 bis 18 Jahren , 1992 .

[30]  R. Stanhope,et al.  Hazards of pharmacological tests of growth hormone secretion in childhood. , 1992, BMJ.

[31]  G. Van Oost,et al.  [Longitudinal physical development of healthy children 0 to 18 years of age. Body length/height, body weight and growth velocity]. , 1992, Klinische Padiatrie.

[32]  P. Hindmarsh,et al.  The use of low doses of ACTH in the investigation of adrenal function in man. , 1991, The Journal of endocrinology.

[33]  M. Lahav,et al.  Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. , 1991, The Journal of clinical endocrinology and metabolism.

[34]  I. Brandt,et al.  [The growth rate of healthy children in the first 16 years: Bonn-Dortmund longitudinal developmental study]. , 1988, Klinische Padiatrie.

[35]  W. Oelkers,et al.  Dose-response relationships between plasma adrenocorticotropin (ACTH), cortisol, aldosterone, and 18-hydroxycorticosterone after injection of ACTH-(1-39) or human corticotropin-releasing hormone in man. , 1988, The Journal of clinical endocrinology and metabolism.

[36]  H. Kehlet,et al.  RE‐EVALUATION OF THE CLINICAL VALUE OF THE 30 MIN ACTH TEST IN ASSESSING THE HYPOTHALAMIC‐PITUITARY‐ADRENOCORTICAL FUNCTION , 1987, Clinical endocrinology.

[37]  T. Mckenna,et al.  Normal cortisol response to corticotropin in patients with secondary adrenal failure. , 1983, Archives of internal medicine.

[38]  J. O'brian,et al.  Discordant cortisol response to exogenous ACTH and insulin-induced hypoglycemia in patients with pituitary disease. , 1982, The New England journal of medicine.

[39]  H. Kehlet,et al.  Reliability of the 30-minute ACTH test in assessing hypothalamic-pituitary-adrenal function. , 1978, The Journal of clinical endocrinology and metabolism.

[40]  G. Besser,et al.  The adrenocortical response to surgery and insulin‐induced hypoglycaemia in corticosteroid‐treated and normal subjects , 1969, The British journal of surgery.